Zifeng Zhuang, Shaozi Lin, Yixuan Li, Xiaokang Xie, Hongling Chen, Yuting Hao, Lan Lin, Guoping Zhao, Di Zhang
{"title":"Methyl eugenol increases neural microcirculation to promote nerve repair by regulating endothelial cell and Schwann cell communication via Ptn/Sdc4","authors":"Zifeng Zhuang, Shaozi Lin, Yixuan Li, Xiaokang Xie, Hongling Chen, Yuting Hao, Lan Lin, Guoping Zhao, Di Zhang","doi":"10.1007/s13659-026-00617-z","DOIUrl":"10.1007/s13659-026-00617-z","url":null,"abstract":"<div><p>Neuromicrocirculatory disorders often accompany nerve injury. Improving neural microcirculation can promote the repair of injured nerves. Methyl eugenol is a major bioactive component of <i>Asarum heterotropoide</i>s and has been reported to exert analgesic effects in chronic pain. This study aimed to demonstrate that methyl eugenol can enhance neural microcirculation and thereby promote nerve repair. A combination of single-cell sequencing and mRNA sequencing revealed that pleiotrophin (Ptn)/syndecan-4 (Sdc4) is vital for coupling between endothelial cells and Schwann cells. A total of 32 rats were randomly assigned to four groups, namely, the Sham, chronic constriction injury (CCI) 7d, CCI 14d, and CCI 21d groups, to assess whether endothelial Schwann cell communication is diminished following CCI. After an endothelial cell–Schwann cell coculture system was established, methyl eugenol, Ptn siRNA, and Sdc4 siRNA were administered. In a separate experiment, 32 SD rats were randomly divided into four experimental groups: the Sham, CCI, ibuprofen, and methyl eugenol groups. CellChat analysis revealed that nerve injury reduced the degree of communication between endothelial cells and Schwann cells, especially communication via Ptn/Sdc4. CCI disrupted neural microcirculation, lowered Ptn levels, and increased Sdc4 expression. In cell experiments, methyl eugenol promoted rat aortic endothelial cells tube formation and increased the release of Ptn, which acted on Sdc4 in rat Schwann cells (RSC96) to promote migration, but did not directly promote RSC96 cell migration in the absence of endothelial cell–derived factors. Treatment with methyl eugenol increased neural microcirculation to promote nerve repair in rats subjected to CCI. In addition, methyl eugenol further increased Ptn levels. CCI led to neural microcirculatory dysfunction and nerve injury. Methyl eugenol promote nerve repair by enhancing neural microcirculation through regulation of endothelial cell and Schwann cell communication via Ptn/Sdc4.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanye Zhang, Yuanhe Wang, Huiyan Shao, Xingli Guo, Pengcheng Xu, Yanlang Li, Jianke Jia, Fawu Dong, Jiang-miao Hu, Liu Yang
{"title":"A self-assembled Dendrobium polysaccharide hydrogel with anti-aging activity via the FOXO signaling pathway","authors":"Yanye Zhang, Yuanhe Wang, Huiyan Shao, Xingli Guo, Pengcheng Xu, Yanlang Li, Jianke Jia, Fawu Dong, Jiang-miao Hu, Liu Yang","doi":"10.1007/s13659-026-00642-y","DOIUrl":"10.1007/s13659-026-00642-y","url":null,"abstract":"<div><p>Faced with the complexity and diversity of skin aging, it is critical to investigate multi-target synergistic anti-aging products. Herein, a novel composite hydrogel with anti-aging activity was developed based on Dendrobium polysaccharide, hyaluronic acid (HA), and nicotinamide (NMN). The hydrogen bond and van der Waals force were the main driving forces in the self-assembly interaction between Dendrobium polysaccharides (DDAM-1 and DOMOS), HA, and NMN. They also were important molecular mechanisms for the gel formation of the composite hydrogel, and the results have been confirmed by ITC and molecular docking. The composite hydrogel demonstrated potent anti-aging effect on the skin in vivo and in vitro, including inhibited elastase/collagenase, promoted type I collagen secretion, prevented ROS, and reduced the expression of IL-6/MMP-3. In addition, the anti-aging mechanism of the composite hydrogel may be associated with FOXO and TGF-β/Smad- SIRT1 signaling pathways mediated by FOXO3, SIRT1, SMAD3 and TGF-β. Briefly, this study demonstrates the potential of HA-infused composite hydrogels for use as anti-aging cosmetic products due to their synergistic anti-aging strategies for anti-aging applications.</p></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Structural characterization and antiviral activity of polysaccharide from Codonopsis pilosula","authors":"Ya-hui Song, Fang-qin Mao, Meng-fan Liu, Zhang-quan Liu, Qing-yan Xin, Lan Yu","doi":"10.1007/s13659-026-00649-5","DOIUrl":"10.1007/s13659-026-00649-5","url":null,"abstract":"<div><p>Codonopsis polysaccharides exhibit diverse biological activities, but their antiviral effects against the H1N1 influenza A virus and how these activities change after sulfation modification remains unclear. In this study, crude Codonopsis polysaccharide (COP) was obtained via water extraction and alcohol precipitation, and COP-1 (2.1 × 103 Da, β-D-(2 → 1)-fructan) was isolated and purified. Both COP and COP-1 were modified by sulfation using the sulfur trioxide-pyridine method, yielding derivatives SCOP and SCOP-1 with degrees of substitution of 1.792 and 1.403, respectively. Antiviral activity was evaluated in MDCK cells using MTT and TCID₅₀ assays, revealing that COP, SCOP, and SCOP-1 all inhibited H1N1 replication, with sulfation significantly enhancing antiviral activity. Time-of-addition experiments indicated that inhibition occurred during the early phase of infection (0–4 h). Annexin V-PI staining confirmed that these compounds reduced virus-induced early apoptosis. In H1N1-infected A549 cells, they suppressed NF-κB p65 phosphorylation and downregulated the expression of <i>IL-6, IL-8, MCP-1, CCL-5, TNF-α</i>, and <i>TRAIL</i>. Overall, Codonopsis polysaccharides and their sulfated derivatives exert anti-influenza effects through a triple mechanism involving inhibition of early viral replication, anti-apoptotic activity, and anti-inflammatory action, making them promising candidates for antiflu therapeutics.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting the tumor microenvironment: a new strategy for natural products in breast cancer therapy","authors":"Yan-Cai Liu, Yan-Ran Yang, Jiang-Long Wang, Hao-Yang Yu, Min Shao, He-Feng Zhou","doi":"10.1007/s13659-026-00641-z","DOIUrl":"10.1007/s13659-026-00641-z","url":null,"abstract":"<div><p>The development and drug resistance of breast cancer are closely associated with the heterogeneity of the tumor microenvironment (TME). Immunosuppressive cells, activated matrix components, abnormal vascular networks, and metabolic reprogramming within the TME collectively create a niche that promotes tumor survival. Despite the clinical adoption of emerging therapies such as immune checkpoint inhibitors, overall response rates remain constrained by the suppressive characteristics of the TME. Natural products, with their multi-component, multi-targeted, and low-toxicity advantages, demonstrate significant potential in reshaping the TME. This systematic review summarizes recent advances in natural products regulating the breast cancer TME. We highlight the molecular mechanisms by which natural products reverse immunosuppression, normalize tumor vasculature, inhibit stromal fibrosis, and correct metabolic dysregulation. Additionally, synergistic strategies combining natural products with chemotherapy and immunotherapy are explored, particularly how nanotechnology-based delivery systems overcome pharmacokinetic barriers. Finally, we critically analyze translational challenges in this field and outline future research directions.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A fungal-derived benzothiazole derivative overcomes osimertinib resistance in NSCLC by targeting SCD1","authors":"Boyin Li, Yuanyu Ke, Jinhua Zhu, Weisong Zhang, Mingjin Yang, Zhan Li, Mu Chen, Zhiling Liu, Jieyao Liu, Qiudi Deng, Peng Zhang, Xueping Lei","doi":"10.1007/s13659-026-00645-9","DOIUrl":"10.1007/s13659-026-00645-9","url":null,"abstract":"<div><p>Osimertinib resistance remains a critical factor for treatment failure in non-small cell lung cancer (NSCLC), making it of great clinical significance to develop novel agents that can overcome this resistance. Natural products are invaluable sources for anti-drug discovery. In this study, we first report that 6-(2-hydroxyethyl) benzo[d]thiazol-4-ol (HBT), a benzothiazole derivative isolated from the endophytic fungus <i>Aspergillus</i> sp. 1022LEF, effectively reverses osimertinib resistance both in vitro and in vivo. Our results demonstrate that HBT effectively inhibits the proliferation of osimertinib-resistant cells by inducing ferroptosis, a novel form of iron-dependent cell death driven by lipid peroxidation. This effect is partially dependent on stearoyl-CoA desaturase 1 (SCD1). Further mechanistic studies revealed that HBT acts as a novel SCD1 inhibitor by directly binding to SCD1 and promoting its degradation, thereby leading to lipid peroxidation and ferroptosis. In vivo experiments showed that HBT treatment significantly suppressed tumor growth in PC9-OR xenograft models, as evidenced by reduced tumor volume and weight. In summary, our study not only identifies HBT as a promising therapeutic candidate for overcoming osimertinib resistance in NSCLC but also suggest that SCD1 is a potential target for combating such resistance.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00645-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanan Wang, Wenjing Wang, Min Zhang, Chenggen Zhu, Chengbo Xu, Xia Li, Xiaoqiang Lei, Qinglan Guo, Jiangong Shi
{"title":"Insight into medicinal chemistry behind traditional Chinese medicines: polybenzyls in Gastrodia elata","authors":"Yanan Wang, Wenjing Wang, Min Zhang, Chenggen Zhu, Chengbo Xu, Xia Li, Xiaoqiang Lei, Qinglan Guo, Jiangong Shi","doi":"10.1007/s13659-026-00625-z","DOIUrl":"10.1007/s13659-026-00625-z","url":null,"abstract":"<div><p>Thirteen undescribed minor polybenzyl constituents included derivatives of six tetrabenzyls (gastrotetrabenzins A−F, <b>1</b>−<b>6</b>), five pentabenzyls (gastropentabenzins A−E, <b>7</b>−<b>11</b>), and two hexabenzyls (gastrohexabenzins A and B, <b>12</b> and <b>13</b>), along with a known pentabenzyl (<b>14</b>), were isolated from an aqueous extract of <i>Gastrodia elata</i> Blume rhizomes (tian ma). Meanwhile, <b>4</b>−<b>10</b> and <b>12</b>−<b>14</b> as well as fourteen undescribed polybenzyls (<b>15</b>−<b>28</b>) and one known analogue (<b>29</b>) were isolated and structurally characterized from a refluxed water solution of <i>p</i>-hydroxybenzyl alcohol. Subsequent UPLC-HRESIMS analysis of the extracts of commercial tian ma and fresh <i>G. elata</i> rhizomes proved that the polybenzyls from the aqueous extract are producible by the traditional application methods of processing and decocting. Bioassays showed that the polybenzyls were much more active than the main constituents<i> p</i>-hydroxybenzyl alcohol and gastrodin of tian ma. These results provide experimental evidences to explain why tian ma is processed and decocted in traditional Chinese medicine (TCM), unravelling structural modification and active optimization behind the TCM application methods.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00625-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ke Ye, Jie Shi, Huimin Wu, Shujie Wang, Zexu Lin, Jiale Sun, Yuwei Chen, Bohao Wang, Rongxuan Wang, Chenglin Jiang, Yi Jiang, Tom Hsiang, Bin Zhu, Lixin Zhang, Xueting Liu, Guoliang Zhu
{"title":"Genome mining guided identification of new furo[3,2-c]pyridones phaeopyridones A–C from the endophytic fungus Phaeobotryon negundinis 12020","authors":"Ke Ye, Jie Shi, Huimin Wu, Shujie Wang, Zexu Lin, Jiale Sun, Yuwei Chen, Bohao Wang, Rongxuan Wang, Chenglin Jiang, Yi Jiang, Tom Hsiang, Bin Zhu, Lixin Zhang, Xueting Liu, Guoliang Zhu","doi":"10.1007/s13659-026-00644-w","DOIUrl":"10.1007/s13659-026-00644-w","url":null,"abstract":"<div><p>Three pairs of new furo[3,2-<i>c</i>]pyridone derivative racemates, named (±)-phaeopyridones A–C (<b>1</b>–<b>3</b>), together with two new compounds, berkeleyamide E (<b>4</b>), and phaeopyranone (<b>5</b>), were isolated from the endophytic fungus <i>Phaeobotryon negundinis</i> 12020, along with three known compounds, (8<i>S</i>,9<i>S</i>)-dihydroisoflavipucine (<b>6</b>), (8<i>S</i>,9<i>R</i>)-dihydroisoflavipucine (<b>7</b>), and sapinopyridione (<b>8</b>), guided by bioinformatics and feature-based molecular networking and fragment-based LC-MS/MS analysis. The chemical structures of these compounds were elucidated by comprehensive spectroscopic analyses and single-crystal X-ray diffraction. Furthermore, a biosynthetic pathway for compounds <b>1</b>–<b>3</b> was proposed, indicating the unique furo[3,2-<i>c</i>]pyridone moiety may be generated by a non-enzymatic intermolecular hemiketal formation reaction. Our research expands the known range of flavipucine alkaloids and highlights the unexplored biosynthetic potential of natural products derived from endophytic fungi.</p></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00644-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuyang Wang, Shaohua Zhang, Rong Geng, Ruiying Wang, Ying Huang, Gang Xu, Lingmei Kong, Yan Li
{"title":"β-carboline derivative Z86 alleviates pulmonary fibrosis via suppressing TGF-β/Smad signaling","authors":"Yuyang Wang, Shaohua Zhang, Rong Geng, Ruiying Wang, Ying Huang, Gang Xu, Lingmei Kong, Yan Li","doi":"10.1007/s13659-026-00628-w","DOIUrl":"10.1007/s13659-026-00628-w","url":null,"abstract":"<div><p>Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant fibroblast proliferation and excessive expression and deposition of extracellular matrix (ECM) by myofibroblasts, ultimately resulting in progressive and irreversible disorder or even loss of the pulmonary function. IPF is incurable with limited therapeutic options and low survival rate, thus the discovery of the therapeutic potential agents for IPF is in urgent need. Here, we identified isopropyl 9-ethyl-1-(naphthalen-1-yl)-9H-pyrido[3,4-b] indole-3-carboxylate (Z86) as a promising bioactive agent against Bleomycin (BLM) induced pulmonary fibrotic mice with the lung abnormalities including histological alteration, accumulation of ECM, as well as markers of EMT (epithelial-mesenchymal transition) were all relieved upon Z86 treatment in C57BL/6 mice. Consistent to the activity in vivo, Z86 decreased TGF-β induced cell migration, fibrotic marker expression, and myofibroblast activation in A549 and HFL1 cells. In further mechanism of action study of Z86 against IPF, we found TGF-β (transforming growth factor β) /Smad2/3 signaling pathway was substantially attenuated in TGF-β treated A549 and HFL1 cells, with remarkably decreased protein level of Smad2/3. Further, we identified Z86 as a novel USP15 inhibitor. Correspondingly, Z86 interacted with USP15, promoted the ubiquitination and degradation of Smad2/3 and disrupted TGF-β/Smad2/3 signaling pathway. Taken together, our findings demonstrated that Z86 suppressed TGF-β induced pulmonary fibrosis in A549 and HFL cells and BLM induced pulmonary fibrotic mice through inhibiting TGF-β/Smad2/3 signaling, and provided the possibility of USP15 inhibitors as the potential drug candidates for idiopathic pulmonary fibrosis.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-026-00628-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Research progress on biosynthesis and regulation of monoterpenoid compounds","authors":"Junchi Zhang, Jiale Cui, Shang Li, Shiya Chu, Ruiqi Liu, Kangyue Wang, Yuzhe Ren, Changyixin Xiao, Jing Yin","doi":"10.1007/s13659-026-00640-0","DOIUrl":"10.1007/s13659-026-00640-0","url":null,"abstract":"<div><p>Monoterpenoids are an important class of plant volatile natural products with broad applications in the food, fragrance, pharmaceutical, and agricultural industries. However, their conventional production largely relies on plant extraction, which is often constrained by low efficiency, high cost, and limited sustainability. Structurally, monoterpenoids can be classified into acyclic, monocyclic, and bicyclic types, and their structural diversity is closely associated with differences in biosynthetic routes and regulatory mechanisms. Their biosynthesis depends on precursor supply from the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways, followed by terpene synthase (TPS)-mediated scaffold formation and subsequent modification reactions. In addition, monoterpenoid accumulation is regulated by multiple factors, including environmental cues, phytohormone signaling, transcriptional regulation, and epigenetic or post-transcriptional control. Meanwhile, substantial progress has been made in the heterologous production of monoterpenoids in microbial platforms such as <i>Escherichia coli</i> and <i>Saccharomyces cerevisiae</i> through metabolic engineering and synthetic biology. This review summarizes recent advances in monoterpenoid biosynthesis, multilevel regulation, and heterologous production, with particular emphasis on major bottlenecks and optimization strategies for sustainable and efficient biomanufacturing.</p></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Min Tan, Rong Xie, Dan Liu, Yao Bai, Zhi-Jun Zhang, Rong-Tao Li
{"title":"Cornepalenins A–D, picrotoxane-type sesquiterpenes from the flowers of Coriaria nepalensis associated with modulation of GABAB receptor–related signaling","authors":"Min Tan, Rong Xie, Dan Liu, Yao Bai, Zhi-Jun Zhang, Rong-Tao Li","doi":"10.1007/s13659-026-00623-1","DOIUrl":"10.1007/s13659-026-00623-1","url":null,"abstract":"<div><p>Three new picrotoxane-type sesquiterpenes (PSTs) cornepalenins A–C (<b>1</b>–<b>3</b>), along with eight known analogues (<b>4</b>–<b>11</b>), were isolated and identified from the flowers of <i>Coriaria nepalensis</i>. In addition, the spectroscopic data and absolute configurations of the known compound cornepalenin D (<b>4</b>) are reported for the first time. Biological evaluation results showed that multiple compounds exhibited certain inhibitory effects on GABA<sub>B</sub> receptor–mediated signaling pathways in both primary cerebellar granule neurons and GABA<sub>B</sub> receptor–overexpressing HEK 293 T cells. Among them, compound <b>6</b> displayed relatively stronger inhibitory activity under stimulation with GABA and baclofen, and was more potent than the positive control CGP54626. The IC<sub>50</sub> value of compound <b>6</b> was 1.41 ± 0.86 μM under GABA stimulation and 1.45 ± 0.55 μM under baclofen stimulation. In addition, mechanistic studies indicated that this compound suppressed the phosphorylation of ERK1/2. Collectively, this study demonstrates that PSTs can modulate GABA<sub>B</sub> receptor–related signaling pathways and provides experimental evidence for their further investigation in central nervous system–related disorders.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><img></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"16 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}